The potential involvement of Notch signaling in NK cell development

Immunol Lett. 2006 Sep 15;107(1):50-7. doi: 10.1016/j.imlet.2006.07.005. Epub 2006 Aug 7.


NK cells constitute an essential element of the innate immune system; however, the cellular and molecular mechanisms that guide their early development are still poorly understood. Here, we demonstrate that in addition to its known crucial role in T cell development, Notch signaling can also be involved in NK cell development. Thus, upon co-culture on OP9 stroma expressing the Notch ligand Delta-like 1 (OP9-DL1), Pax5-deficient pro-B cells, which have multi-lineage potential, efficiently differentiate into T and NK cells. Upon DL-1 signaling, Pax5-deficient pro-B cells down-regulate both surface CD93 expression and transcripts for B cell-specific genes and concomitantly up-regulate T lineage gene transcripts. Subsequent transfer of DL-1-signaled Pax5-deficient pro-B cells onto OP9 stroma in the presence of IL-2 leads to their efficient differentiation into NK1.1(+), functional NK cells. Moreover, bone marrow early progenitor with lymphoid and myeloid differentiation potential (EPLM), which we have previously described as the normal in vivo-equivalent of Pax5-deficient pro-B cells, also gain the ability to differentiate into effector NK cells following transient DL1 Notch-mediated signaling. The potential involvement of Notch signaling in the generation of the NK cell repertoire in vivo is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Coculture Techniques / methods
  • Down-Regulation
  • Female
  • Flow Cytometry / methods
  • Gene Expression Regulation / physiology
  • Interleukin-2 / physiology
  • Interleukin-7 / physiology
  • Intracellular Signaling Peptides and Proteins / physiology
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / physiology
  • Membrane Proteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Multipotent Stem Cells / physiology*
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism
  • PAX5 Transcription Factor / genetics
  • PAX5 Transcription Factor / metabolism*
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / physiology
  • Receptors, Notch / physiology*
  • Thymus Gland / immunology


  • Dll3 protein, mouse
  • Interleukin-2
  • Interleukin-7
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily D
  • Notch1 protein, mouse
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Receptor, Notch1
  • Receptors, Notch